Jonathan Collin, MD
Aspirin Fails to Prevent Invasive Disease-Free Events in Breast Cancer
It has been commonly accepted that aspirin has been helpful in preventing progression in non-metastatic breast cancer. This knowledge has been based primarily on observational studies that have shown a reduction in breast cancer events, including breast tumor recurrence, invasive breast cancer, and metastasis when using aspirin. Most of these reports have been based on aspirin use in cardiovascular settings where aspirin has been shown to reduce atherosclerotic events due to its anti-inflammatory and anti-platelet activity. Small observational studies have also observed benefit of aspirin use in preventing events in breast cancer patients. However, a recent study—the Alliance trial, led by Chen and colleagues—reported in the April 29, 2024 issue of JAMA that aspirin failed to prevent invasive disease-free events in breast cancer.1
The randomized, double-blinded study evaluated 3020 individuals (3004 women and 16 men) at 534 community and academic sites in the U.S. and Canada. The aspirin group was asked to use 300 mg of aspirin daily. A high level of compliance was observed in aspirin and placebo use; interestingly, there was a similar level of adverse events with both placebo and aspirin use (275 grade 3 adverse events; 130 in aspirin group, 145 in placebo group; 35 grade 4 events; 15 in aspirin group, 20 in placebo group). While the study was planned for 5 years, it was terminated early at the time of the first “safety analysis” (median follow-up 33.8 months, range 0.1-72.6) due to “futility.” There was a statistically insignificant increase of events in the aspirin cohort compared to the placebo arm: 144 vs 112 invasive disease-free events in the aspirin vs the placebo group (Hazard Ratio, 1.27; 95% CI, 0.99-1.63; P=0.06).
Should this study end the recommendation of aspirin use in preventing breast cancer recurrence? Chen and her colleagues would argue “yes” despite the “conventional thinking” that it offers some cancer prevention. Of course, those breast cancer patients who are at high risk for cardiovascular disease should continue their aspirin use if so advised. Additionally, aspirin has been recommended for prevention of other medical conditions, including certain colon cancers. However, the benefit and risk need to be evaluated in older adults who may be at risk for gastrointestinal bleeding.
Prevention of cancer progression remains an area of great importance in cancer care. Establishing the effectiveness of pharmaceuticals, nutraceuticals, and herbals in cancer prevention obligates large placebo-controlled studies of humans and cannot depend on secondary observational studies.
Reference
1. Chen WY, Ballman KV, Partridge AH, et al. Aspirin vs placebo as adjuvant therapy for breast cancer: The Alliance A011502 randomized trial. JAMA. Published online April 29, 2024. doi:10.1001/jama.2024.4840 https://jamanetwork.com/journals/jama/fullarticle/2818110#xd_co_f=YWE5NzVjYTYtYTNjMy00ZTU1LWE4ZjEtYTc4ZGJjOWJhMzA5~
Published June 15, 2024